Peptide antagonists of substance P

Abstract

Undecapeptides retaining the amino acids in positions 2, 3, 4, 5, 6, 8 and 10 of substance P (Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-Phe7-Phe8-Gly9-Leu10-Met11-NH2), but having substitutions in positions 1, 7, 9 and 11 of substance P have been discovered to have high antagonistic activity to block substance P in biological systems. Exemplifying these potent antagonists is D-Arg1,D-Trp7,D-Trp9-Leu11-Substance P, which is an effective inhibitor and has high potency. These antagonists of substance P are useful to elucidate some biological mechanisms of substance P, and to treat inflammatory responses in the eye for medical practice in ophthalmology, and to be novel analgesic agents for medical applications.

What is claimed: 
     
       1. [D-Arg 1 ,D-Trp 7 ,D-Trp 9 ,Leu 11  ]-Sp. 
     
     
       2. [D-Phe 5 ,D-Trp 7 ,D-Trp 9 ,Leu 11  ]-SP 5-1l . 
     
     
       3. Substance P having amino acid substitutions at one or more of positions 1, 2, 5, 7, 9, or 11, wherein the amino acid substitution at position 1 is D-Arg; position 2 is D-Pro; position 5 is D-Phe; position 7 is D-Trp; position 9 is D-trp; and position 11 is Leu. 
     
     
       4. The substituted Substance P of claim 3 which is [D-Arg 1 , D-Pro 2 , D-Phe 5 , D-Trp 7 , D-Trp 9 , Leu 11  ]-SP. 
     
     
       5. The substituted Substance P of claim 3 which is [D-Arg 1 , D-Pro 2 , D-Trp 7 , D-Trp 9 , Leu 11  ]-SP. 
     
     
       6. The substituted Substance P of claim 3 which is [D-Pro 2 , D-Trp 7 , D-Trp 9 , Leu 11  ]-SP. 
     
     
       7. The substituted Substance P of claim 3 which is [D-Trp 7 , D-Trp 9 , Leu 11  ]-SP.